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Both iron overload and iron deficiency have been reported in obesity and metabolic syndromes. Due to the presence of multiple intracellular iron pools and the dynamic nature of iron mobilization and use, the actual status and contribution of free and metabolically active iron toward metabolic syndrome remain to be established. The discovery of nuclear receptor coactivator 4 (NCOA4) as a ferritinophagy receptor provides an opening to address the connection between iron and metabolic diseases. This study aims to specifically dissect the role of hepatic ferritinophagy in lipid metabolism and hepatic steatosis. We conducted a series of Ncoa4 gain‐ and loss‐of‐function experiments to examine how ferritinophagy affects lipid metabolism through phenotypic and lipidomic analyses both in vitro and in vivo. We show that ferritinophagy is required to release iron from ferritin cages for biological use, and is induced by lipid loading in vitro and during the development of obesity in vivo. Ncoa4 knockdown impairs mitochondrial morphology and reduces palmitate‐induced lipid droplet formation in cultured cells and the development of hepatic steatosis in obese mice models. Importantly, the effect of Ncoa4 deficiency on mitochondrial morphology and lipid accumulation is specifically linked to lipidomic reductions in unsaturated fatty acid content in triglycerides and cardiolipins, and an external supply of unsaturated fatty acids reverses these phenotypes. Conclusion: This study shows that ferritinophagy‐derived iron supports fatty acid desaturation and the synthesis of unsaturated fatty acid–rich lipids to reduce lipotoxicity. However, the continuous activation of ferritinophagy contributes to the development of hepatic steatosis and liver damage in obesity. [ABSTRACT FROM AUTHOR]

Anoikis is proved to play a crucial role in the development of cancers. However, the impact of anoikis on the prognosis of bladder cancer (BLCA) is currently unknown. Thus, this study aimed to find potential effect of anoikis in BLCA. The Cancer Genome Atlas (TCGA)-BLCA and GSE13507 cohorts were downloaded from TCGA and the Gene Expression Omnibus (GEO) databases, respectively. Differentially expressed genes (DEGs) were screened between BLCA and normal groups, which intersected with anoikis-related genes to yield anoikis-related DEGs (AR DEGs). Univariate COX, rbsurv, and multivariate COX analyses were adopted in order to build a prognostic risk model. The differences of risk score in the different clinical subgroups and the relevance between survival rate and clinical characteristics were explored as well. Finally, chemotherapy drug sensitivity in different risk groups was analyzed. In total, 78 AR DEGs were acquired and a prognostic signature was build based on the 6 characteristic genes (CALR, FASN, CSPG4, HGF, INHBB, SATB1), where the patients of low-risk group had longer survival time. The survival rate of BLCA patients was significantly differential in different groups of age, stage, smoking history, pathologic-T, and pathologic-N. The IC50 of 56 drugs showed significant differences between 2 risk groups, such as imatinib, docetaxel, and dasatinib. At last, the results of real time quantitative-polymerase chain reaction (RT-qPCR) demonstrated that the expression trend of CALR, HGF, and INHBB was consistent with the result obtained previously based on public databases. Taken together, this study identified 6 anoikis-related characteristic genes (CALR, FASN, CSPG4, HGF, INHBB, SATB1) for the prognosis of BLCA patients, providing a scientific reference for further research on BLCA., Competing Interests: The authors declare there is no potential conflict of interests., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: T2DM with NAFLD is a common disorder of glucose and lipid metabolism affecting the quality of life of patients. Due to the limitations and adverse reactions of drug treatment, acupuncture has been proved to be an effective method for the treatment of T2DM with NAFLD. This study aims to evaluate the efficacy and safety of acupuncture in the treatment of NAFLD in T2DM class, and to provide high-quality evidence for acupuncture in the treatment of this disease., Methods: From establishment of the database to 31 July 2021, We will search the Cochrane Central Register of controlled trials, PubMed, MEDLINE, EMBASE, Web of science. Five Chinese databases, including China National Knowledge Infrastructure (CNKI), WanFang database, VIP, Chinese Biomedical Literature Database (CBM) and the Chinese clinical trial registry. There are no restrictions on language or publication, and they are independently screened and collected by two reviewers. Review Manager 5.3 software will be used for meta analysis. If necessary, heterogeneity testing, data synthesis, and subgroup analysis will be performed., Results: The effectiveness and safety of acupuncture in the treatment of T2DM with NAFLD will be assessed by the outcomes of test's, including: imaging indicators, biomarkers of hepatic steatosis, serological indicators of hepatic fibrosis, improvement of serum NAFLD liver fat score, BMI, blood glucose indexes, blood lipid indexes, insulin level and safety indicators., Conclusion: This meta-analysis will further determine the beneficial efficacy and safety of acupuncture for T2DM combined with NAFLD., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)